cortico-hippocampus circuits & memory consolidation/reconsolidation

retrograde amnesia

loss of memory for details or events before a trauma; usually impairs declarative memory, not procedural

temporary retrograde amnesia

sometimes, lost memories return slowly, but temporary loss is due to retrieval access, not destruction of the memory trace

anterograde amnesia

inability to form new memories usually caused by damage to the brain from trauma or severe alcohol use disorder; typically irreversible

patient H.M.

patient with severe epilepsy that underwent surgery to remove parts of his medial temporal lobe where his seizures originated. He developed severe anterograde amnesia and showed some retrograde amnesia, but could remember experiences from early childhood up to 3 years before the surgery

H.M. summary

impaired episodic memory, intact procedural memory, and intact working memory

Patient C.W.

Clive Wearing has herpesviral encephalitis which caused damage to the hippocampus. He has both retrograde and anterograde amnesia and experiences waking up every 20 seconds or so. He can acquire new procedural memories due to preservation of the parietal cortex but cannot remember the act of learning them

consolidation and encoding

the process by which a memory is stored in the brain

hebbian rule

cells that fire together wire together

proteins

the formation of new memories requires the formation of new proteins to strengthen the connections between brain cells

glutamate

major excitatory neurotransmitter in the brain that is involved in learning and memory

glutamate receptors

strong stimulation of a synapse activates AMPA and NMDA

long-term potentiation

increase in synaptic strength following high frequency stimulation of a synapse which leads to the insertion of more glutamate receptors into the post-synaptic membrane

long-term potentiation (LTP)

thought to underlie how long-term memories are formed; strong stimulation activates both AMPA and NMDA receptors, which results in insertion of more AMPA receptors onto the post-synaptic membrane. So, the next time the pre-synaptic cell is activated, the post-synaptic cell can respond even more

how LTP works

more glutamate receptors means more excitation (depolarization) and the post-synaptic cell will have an even bigger response the next time an action potential comes its way from the presynaptic cell

systems consolidation

the process by which the hippocampus transfers memories to the PFC;

the hippocampus is important for consolidating recent memories and the prefrontal cortex is important for processing “remote” memories from weeks, months, or years ago

recent memories

the hippocampus is highly active when recalling a recent memory

remote memories

prefrontal cortex is highly active when recalling a remote memory

memory extinction

the process by which an organism learns to suppress a memory, also require protein synthesis and subregions of the PFC are highly active when making an extinction memory

prelimbic cortex (PL)

highly active during heightened states of fear, including the return of fear after extinction

infralimbic cortex (IL)

highly active during the suppression of fear

memory reconsolidation

process of previously consolidated memories being recalled and actively consolidated again; serves to maintain, strengthen, and modify memories that are already stored in long-term memory

reconsolidation vulnerability

process where stored memories become destabilized or labile and susceptible to modification

consolidation and reconsolidation both require protein synthesis

administering protein synthesis blockers like anisomycin during consolidation or reconsolidation blocks LTM; in both cases, the memory appears to be come

short term memory / active state

lasts seconds to hours, sensitive to disruption, does not require protein synthesis

long term memory / inactive state

lasts days to weeks, not sensitiv to disruption, does require protein synthesis

reinstate

giving an animal a reminder shock actually unmasks the fear memory and causes it to come back

extinction-reconsolidation in humans

humans first form memories on day 1

day 2, they’re given a brief reminder to open up the reconsolidation window, followed by a 10 min or 6 hour delay

all groups then receive extinction trials

giving extinction trials 10 minutes after the reminder cue during the reconsolidation window erased the memory